title: Progression-free survival as a surrogate for overall survival in advanced/recurrent gastric cancer trials: a meta-analysis.
abstract: The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval [CI] = 0.852 to 0.854). The R (2) between treatment effects on PFS and on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were only moderately correlated, and we could not confirm the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cancer.
authors.affiliation: Affiliations of authors: Biostatistics Department, INSEM U900 Institut Curie, Paris, France (XP); Translational Research and Clinical Trial Center, Hokkaido University Hospital, Hokkaido, Japan (KO); Seoul National University College of Medicine, Oncology Division, Seoul, Korea (Y-JB); Jules Bordet Hospital, Brussels, Belgium (HB); St. Marianna University School of Medicine, Kawasaki, Japan (NB); Hôpital Robert Debré, Reims, Department of Clinical Oncology, France (OB); Dana-Farber Cancer Institute and Harvard School of Public Health, Department of Biostatistics, Boston, MA (PC); National Cancer Center Hospital East, Department of Gastrointestinal Oncology, Kashiwa, Japan (NF, AO); Institut Gustave Roussy, Université Paris XI, Biostatistics and Epidemiology Department, Villejuif, France (SMi); Johannes Gutenberg University, Medical Department, Mainz, Germany (MM); Yokohama City University, Department of Biostatistics and Epidemiology, Kanagawa, Japan (SMo); University of Tokyo, Tokyo, Japan (YO); University Hospital, Department of Surgery, Geneva, Switzerland (AR); University Hospital Europeen Georges Pompidou, Gastro-enterology Department, Paris, France (PR); Tokai Central Hospital, Sohara, Japan (JS); Mayo Clinic, Division of Biomedical Statistics and Informatics, Rochester, MN (DS); National Cancer Center Hospital East, Kashiwa, Japan (MS); Aichi Cancer Center Hospital, Department of Gastrointestinal Oncology, Aichi, Japan (KS); Charité-Universitätsmedizin Berlin, Department of Haematology, Oncology, and Tumorimmunology, Berlin, Germany (PT-P); University Hospital Gasthuisberg, Digestive Oncology Unit, Leuven, Belgium (EVC); Hasselt University, Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Diepenbeek, Belgium (TB, MB); International Drug Development Institute, Louvain-la-Neuve, Belgium (MB).
authors.forename: Xavier
authors.initials: X
authors.lastname: Paoletti
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Harry
authors.initials: H
authors.lastname: Bleiberg
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.forename: Paul
authors.initials: P
authors.lastname: Catalano
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Arnaud
authors.initials: A
authors.lastname: Roth
authors.forename: Philippe
authors.initials: P
authors.lastname: Rougier
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Daniel
authors.initials: D
authors.lastname: Sargent
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sasako
authors.forename: Kohei
authors.initials: K
authors.lastname: Shitara
authors.forename: Peter
authors.initials: P
authors.lastname: Thuss-Patience
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Tomasz
authors.initials: T
authors.lastname: Burzykowski
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
mesh_terms: D015415:Biomarkers; D018572:Disease-Free Survival; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000628:therapy*; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers